SDH deficient paraganglioma-pheochromocytoma is an inherited condition. Paraganglia are groups of non-neuronal cells that are found
near nerve cell bunches called ganglia. A tumor involving the paraganglia is known as a paraganglioma. A type of paraganglioma known as a pheochromocytoma develops in the adrenal glands, which are
located on top of each kidney and produce hormones in response to stress. Other types of paragangliomas can also delelop in the head, neck, or trunk. People with hereditary
paraganglioma-pheochromocytoma are susceptable to development types of paragangliomas, which may include pheochromocytomas. In the case of Carney-Stratakis dyad, patients may develop paragangliomas
as well as GIST tumors.
Pheochromocytomas and some paragangliomas are associated with ganglia of the sympathetic nervous system. The sympathetic nervous system
controls the "fight-or-flight" response, a series of changes in the body due to hormones released in response to stress. Sympathetic paragangliomas found outside the adrenal glands, usually in the
abdomen, are called extra-adrenal paragangliomas. Most sympathetic paragangliomas, including pheochromocytomas, produce hormones called catecholamines, such as epinephrine (adrenaline) or
norepinephrine. These excess catecholamines can cause signs and symptoms such as high blood pressure (hypertension), episodes of rapid heartbeat (palpitations), headaches, or
Most paragangliomas are associated with ganglia of the parasympathetic nervous system, which controls involuntary body functions such as
digestion and saliva formation. Parasympathetic paragangliomas, typically found in the head and neck, usually do not produce hormones. However, large tumors may cause signs and symptoms such as
coughing, hearing loss in one ear, or difficulty swallowing.
Although some paragangliomas and pheochromocytomas are noncancerous, some can metastasize to other parts of the body. Extra-adrenal
paragangliomas associated with the presence of an SDH gene mutation have a more malignant potential than other types of paraganglioma or pheochromocytoma. Patients who’ve had a tumor should be
monitored yearly in case of metastasizes. Hereditary paraganglioma-pheochromocytoma is typically diagnosed in a person's 30s. Hereditary paraganglioma-pheochromocytoma occurs in approximately 1 in 1
Mutations in the SDHB, SDHC, SDHD, and SDHAF2 genes lead to the loss or reduction of SDH enzyme activity. Because the mutated SDH enzyme
cannot convert succinate to fumarate, succinate accumulates in the cell. As a result, the hypoxia pathways are triggered in normal oxygen conditions, which lead to abnormal cell growth and tumor
Paragangliomas and pheochromocytomas can occur in individuals with other inherited disorders, such as von-Hippel Lindau syndrome and
certain types of multiple endocrine neoplasia. These other disorders feature additional tumor types and have different genetic causes. Some paragangliomas and pheochromocytomas occur in people with
no history of the tumors in their families and appear not to be inherited. These cases are designated as sporadic.